TB: The Coventry perspective Dr Thekli Gee University Hospitals Coventry & Warwickshire

Outline TB in Coventry: Epidemiology Resources New diagnostic approaches

Epidemiology

Occurrence Nearly a third of the world’s population is infected with TB TB kills almost 3 million people per year. In the mid-1980s, a resurgence of outbreaks in the U.S. brought renewed attention to TB. Since 1985, the incidence of TB in the general population has increased 14% reversing a 30 year downward trend. In 1993, over 25,000 new cases of TB were reported in the U.S. During 1994 and 1995, however, there was a decrease in TB cases in the U.S. likely due to increased awareness and efforts in prevention and control of TB.

Tuberculosis notifications England & Wales 1913 - 2006 chemotherapy BCG vaccination Source: Statutory Notifications of Infectious Diseases (NOIDs)

Coventry TB rate by year 1999-2006 2007 Rate per 100,000 population 5 10 15 20 25 30 35 1999 2000 2001 2002 2003 2004 2005 2006 rate Coventry PCT West Midlands England & Wales Linear (Coventry PCT)

Tuberculosis case reports and rates by region/country, England, Wales and Northern Ireland, 2006 Coventry 2007

Coventry

Why Is TB Increasing? These factors contribute to the growing increase in TB cases.

Why Is TB Increasing? Multiple contributing factors: Homelessness Intravenous drug use HIV infection Drug-resistant strains of TB Reduced TB control and treatment resources Immigration from high TB prevalence areas These factors contribute to the growing increase in TB cases.

Tuberculosis case reports by place of birth and ethnic group, England, Wales and Northern Ireland, 2001 - 2006

Changing populations Coventry City council Coventry refugee centre 1215 asylum seekers on housing list Coventry refugee centre 8000 asylum seekers & refugees registered 1571 registered at Meridian Health Centre

Changing populations Afghanistan Iraq Iran Burundi Democratic Republic of Congo Ethiopia Eritrea Somalia Sudan Zimbabwe

Resources Increasing numbers of TB cases  Increased demand on TB services

Impact on resources Hospital & community TB services Infection control TB clinic TB nurse time Infection control Isolation facilities TB incidents Occupational health Pre-employment screening HCW contacts Laboratory services

Impact on resources Hospital & community TB services Infection control TB clinic TB nurse time Infection control Isolation facilities TB incidents Occupational health Pre-employment screening HCW contacts Laboratory services

TB incidents at UHCW NHS Trust 23 incidents in since January 2007 18 Patients Not isolated early enough / at all during admission Mostly medical wards 2 Cardiothoracic ward 1 haematology day unit 5 Health care workers 3 qualified nurses 1 nursing student Ward host

Impact on resources Hospital & community TB services Infection control TB clinic TB nurse time Infection control TB incidents Isolation facilities Occupational health Pre-employment screening Annual reminders HCW contacts Laboratory services 2007

Impact on resources Hospital & community TB services Infection control TB clinic TB nurse time Infection control TB incidents Isolation facilities Occupational health Pre-employment screening Annual reminders HCW contacts Laboratory services 2006

TB national strategy 2004 2007 2006 2007

Controlling TB: Diagnosing primary cases Treating active disease Preventing transmission Identifying secondary cases Controlling latent infection We began by looking at some of the reasons why a guideline on TB was produced. TB is a growing problem in England and Wales, and without proper treatment and contact tracing the spread of the disease will increase. This is a particular risk when drug resistant strains are being treated, or if incomplete treatment leads to an increase in multidrug-resistant strains. The guideline affect patients in hospitals and prison services as well as in the community. Staff involved in implementing it will need appropriate training, and confidence in their ability to perform their roles. Successful implementation will involve many different teams and services working together, and each one has an important role to play. The TB guideline deals with activities undertaken by different professionals in the NHS, with multiple aims: to diagnose primary cases, to identify secondary cases, to treat active disease, to control latent infection, and to prevent further transmission. The combined result of these activities should be to curb and reverse the increase in TB incidence seen in England and Wales in recent years

Current diagnostic test for latent TB Diagnosis of latent TB relies on the tuberculin skin test. 101 years old Developed 1907 by Charles Mantoux The oldest diagnostic test still in use. The skin test enters its 6th decade of use. (Canada 1957)

Tuberculin skin tests Mantoux test Heaf test 48-72 hours later No longer available

Tuberculin skin tests Poor specificity: Poor sensitivity: antigenic cross-reactivity BCG environmental mycobacteria Poor sensitivity: 75-90% in active disease lower in disseminated TB and HIV infection Need for return visit 50% DNA rate Operator variability inoculation & reading Painful inflammation & scarring Boosting effect if used repeatedly

New approaches

TB Interferon-g release assays (TIGRA) Principle of TIGRA Detect IFN-g produced by effector T-cells that recognise M. tuberculosis proteins ESAT-6 & CFP-10 Absent in BCG Absent in most non-tuberculous Mycobacteria Exceptions: M. marinum, M. kansasii

Two Tests available T-Spot.TB® QuantiFERON Gold® Detects individual effector T-cells that produce IFN-g in response to M.tuberculosis antigens Enzyme linked immunospot technique (ELISPOT). QuantiFERON Gold® Measures IFN-g in the supernatant of the antigen stimulated cells Enzyme linked immunosorbant assay technique (ELISA)

T-Spot.TB® Quantiferon Gold® Sensitivity Immunocompetent 83-97% 70-89% Immunocompromised + malnourished + children <1% indeterminate results 20-24% indeterminate results

T-Spot.TB® Quantiferon Gold® Sensitivity Immunocompetent 83-97% 70-89% Immunocompromised + malnourished + children <1% indeterminate results 20-24% indeterminate results Specificity 99.99% 98%

T-Spot.TB® Quantiferon Gold® Sensitivity Immunocompetent 83-97% 70-89% Immunocompromised + malnourished + children <1% indeterminate results 20-24% indeterminate results Specificity 99.99% 98% Cost (including labour etc) £55-60 per test £30

<1% indeterminate results 20-24% indeterminate results T-Spot.TB® Quantiferon Gold® Sensitivity Immunocompetent 83-97% 70-89% Immunocompromised + malnourished + children <1% indeterminate results 20-24% indeterminate results Specificity 99.99% 98% Cost (including labour etc) £55-60 per test £30 Problems Must process within 8 hours of venepuncture Expertise in cell separation -in tube assay? Not reliable enough in the Immunocompromised & children

Method - T-Spot.TB® Specimens must be processed within 8 hours of venepuncture

ELISPOT -ve +ve

ELISPOT Reader

Role of TIGRAs Detection of latent TB: TB contacts Healthcare workers New employment screens Following TB exposure incidents Before starting immunosuppression anti-TNF-α drugs e.g infliximab Pre-transplantation Detection of active extra-pulmonary TB If difficult to diagnose by conventional methods Closely competing diagnoses e.g. Sarcoid vs TB

Contact tracing: When to use a TIGRA NICE: Following positive Mantoux test Most cost effective May miss some cases CDC In place of Mantoux test Shifts burden of work from TB nurses to lab

Business case Laboratory service TIGRA 5 day to 6 day service Warwickshire wide (Network) TIGRA Tspot.TB Microbiology / Immunology

Summary TB increasing in Coventry Increased demand on resources New approaches considered e.g. TIGRAs